A vein attempt: Debris from angioplasty good for proteomics

Ezine

Published: Jul 16, 2012

Author: Steve Down

Channels: Proteomics & Genomics / Proteomics

Collecting debris from angioplasty

Atherosclerosis and thrombosis are two major contributors to heart disease but the former can lead to the latter. During atherosclerosis, fat deposits known as plaque build up on the inner walls of the arteries causing them to narrow, so restricting the flow of blood and forcing the heart to work harder. Occasionally, the plaque breaks up, sending loosened material free in the artery where it can induce sudden and dangerous blockages, known as thromboses.

One of the conventional treatments of atherosclerosis is angioplasty, in which blocked or narrowed arteries are widened by inserting short tubes, known as stents. A small balloon is inserted into the stent and inflated to push the stent against the artery walls and squash the plaque, to allow the blood to flow more freely. However, this operation can dislodge plaque material which might cause problems such as thrombosis. So, a special piece of kit known as a distal embolic protection device (DEPD) is also inserted to capture these fragments and prevent damage.

The trapped matter in the DEPD consists of proteins and lipids from the atherosclerotic area, so it might hold information which would help to understand the disease. A team of scientists in Spain has recognised the potential of this material and studied it by proteomics to try and gain more insight into the biological basis of plaque formation and break up.

José Castillo and colleagues from the University of Santiago de Compostela, the Autonomous University of Madrid, the Doctor Josep Trueta University Hospital of Girona, and the Germans Trias i Pujol University Hospital in Barcelona, wanted to follow up the proposal that systemic inflammation can destabilise the plaque. This theory is gaining in popularity and the team decided to look for protein signals suggesting that systemic inflammation is taking place in atherosclerotic patients.

Inflammatory search

The material was collected from DEPDs of 23 patients who had undergone angioplasty of the carotid arteries, which are located on each side of the neck and supply blood to your brain. The patients were classified as having either reduced or high systemic inflammation, which was assessed by measuring the levels of C-reactive protein in their serum.

This protein is an established marker of inflammation and is used to monitor therapies for atherosclerotic plaque, as well as to predict stroke and heart attack. Its expression has been linked with the progression of atherosclerosis and it triggers the expression of another group of proteins, matrix metalloproteinases, which help to destabilise the plaque and cause it to break up.

Proteins in the DEPD material were separated by 2D gel electrophoresis and the gels for each sample were compared. The protein spots with different abundances were removed to identify the proteins by mass spectrometry.

The results obtained by analysing the DEPD debris were corroborated by immunohistochemical examination of plaque that had been surgically removed, to check the viability of using the debris to study atherosclerosis, although the validation study was carried out on a different set of samples to those used in the proteomics evaluation.

Novel protein source for proteomics

An average of 370 proteins spots were observed on the gels, with some notable features. The abundances of seven proteins were altered by the level of systemic inflammation in the patients. Five were more abundant in patients with high systemic inflammation and two were up-regulated in patients with low systemic inflammation.

Three proteins were corroborated by immunohistochemistry. One was annexin A5, which was raised in the plaque debris from patients with high inflammation. This protein has many functions, including the modulation of inflammatory and immune functions, so it could be over-expressed in order to protect against the vascular inflammation and remodelling that accelerates atherosclerosis.

Glutathione S-transferase kappa 1 was more abundant in patients with lower inflammation and the research team speculated that it could help to protect the walls of the veins against oxidative damage because it is known to detoxify low density lipoprotein and reactive oxygen species. The third validated protein was transgelin-2 whose function is unclear although it has been linked to the progression of atherosclerosis.

This study has illustrated that the material recovered from DEPDs after angioplasty is suitable for proteomics studies and can be used to search for biomarkers of atherosclerosis to help understand the disease. Protein abundances are affected by inflammation but the validity of the biomarkers cannot be established until a far greater number of samples has been analysed.

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